Intrathecal ropivacaine 5 mg/ml for outpatient knee arthroscopy: a comparison with lidocaine 10 mg/ml.
The aim of this prospective, randomised, blind study was to compare the evolution of spinal block produced with 50 mg lidocaine 10 mg/ml and 10 mg ropivacaine 5 mg/ml for outpatient knee arthroscopy. Thirty outpatients undergoing knee arthroscopy received 50 mg of lidocaine 10 mg/ml (n=15) or 10 mg of ropivacaine 5 mg/ml (n=15) intrathecally. The evolution of spinal block was recorded until home discharge, while the occurrence of transient neurologic symptoms (TNS) was evaluated through phone-call follow-ups. The median onset time was 15 (10-21) min with lidocaine and 24 (11-37) min with ropivacaine (P=0.109). Spinal lidocaine resulted in a faster resolution of sensory block [148 (130-167) min vs. 188 (146-231) (P=0.022)], unassisted ambulation with crutches [176 (144-208) min vs. 240 (179-302) min (P=0.014)], and voiding [208 (163-254) min vs. 293 (242-343) min (P=0.001)] than ropivacaine. Recovery of motor function required 113 (95-131) min with lidocaine and 135 (87-183) with ropivacaine (P=0.219). Six lidocaine patients reported TNS (40%) as compared with no patient receiving ropivacaine (0%) (P=0.005). Spinal block produced with 10 mg ropivacaine 5 mg/ml is as effective as that produced by 50 mg of lidocaine 10 mg/ml. Recovery of unassisted ambulation and spontaneous voiding occurred earlier with lidocaine, but this was associated with a markedly higher incidence of TNS.


[Improve, but measure in moderation; quality management in specialty residency training].
Intuitively, we believe we gain knowledge through taking measurements, and our appetite for quality measurement in general has grown spectacularly. However, this approach has to be qualified. Many aspects of quality are difficult to measure, yet are very important, and choosing what to measure may be heavily influenced by the availability bias of instruments. Moreover, a lot can be known without actually measuring. Quantitative results tend to offer false reassurance simply by their abundance, and results presented by means of Likert scales may obscure the crucial critique of a minority of respondents. Narrative comments in surveys are often much more meaningful as they can foster an open dialogue between residents and their clinical teachers, preferably led by a neutral chairperson. Contrary to what is often claimed, it is even possible to engage in improvement without prior measurement. I propose measuring only in moderation and instead devoting time and money to patient care and educating residents, and on the design and execution of improvement plans.


Venocclusive disease of the liver after bone marrow transplantation: the role of hemostasis.
Venocclusive disease of the liver is a relatively frequent early complication of bone marrow transplantation related to pre-transplant toxic injury to the liver. Events that lead to toxicity of the liver in the pre-transplant setting are infection, anti-neoplastic and anti-infectious drug administration and radiation. The histological correlates of venocclusive disease are lesions mainly localized to structures in zone 3 of the liver acinus and in the sublobular central venules. At some point in the pathogenesis of venocclusive disease, blood clotting and inflammation occur. The first is characterized by laboratory signs of coagulation activation, by an increase in several procoagulant proteins and by a decrease in naturally occurring anticoagulants, particularly protein C, the latter being a sensitive index of liver injury. Inflammation is mediated by cytokine production, which maintains procoagulant endothelial responses and liver injury. Severe venocclusive disease is associated with multi-organ failure and elevated mortality. Attempts at finding predictive markers of the disease have succeeded in identifying some coagulation and inflammatory proteins which can be useful in predicting the occurrence of VOD in selected patient groups. The role of hemostasis in venocclusive disease is underscored also by the reports on the successful prophylaxis and management of the disease with heparin and thrombolytic agents.


YAP integrates the regulatory Snail/HNF4α circuitry controlling epithelial/hepatocyte differentiation.
Yes-associated protein (YAP) is a transcriptional co-factor involved in many cell processes, including development, proliferation, stemness, differentiation, and tumorigenesis. It has been described as a sensor of mechanical and biochemical stimuli that enables cells to integrate environmental signals. Although in the liver the correlation between extracellular matrix elasticity (greatly increased in the most of chronic hepatic diseases), differentiation/functional state of parenchymal cells and subcellular localization/activation of YAP has been previously reported, its role as regulator of the hepatocyte differentiation remains to be clarified. The aim of this study was to evaluate the role of YAP in the regulation of epithelial/hepatocyte differentiation and to clarify how a transducer of general stimuli can integrate tissue-specific molecular mechanisms determining specific cell outcomes. By means of YAP silencing and overexpression we demonstrated that YAP has a functional role in the repression of epithelial/hepatocyte differentiation by inversely modulating the expression of Snail (master regulator of the epithelial-to-mesenchymal transition and liver stemness) and HNF4α (master regulator of hepatocyte differentiation) at transcriptional level, through the direct occupancy of their promoters. Furthermore, we found that Snail, in turn, is able to positively control YAP expression influencing protein level and subcellular localization and that HNF4α stably represses YAP transcription in differentiated hepatocytes both in cell culture and in adult liver. Overall, our data indicate YAP as a new member of the HNF4/Snail epistatic molecular circuitry previously demonstrated to control liver cell state. In this model, the dynamic balance between three main transcriptional regulators, that are able to control reciprocally their expression/activity, is responsible for the induction/maintenance of different liver cell differentiation states and its modulation could be the aim of therapeutic protocols for several chronic liver diseases.


Neuropeptide Y (NPY) inhibits spontaneous contraction of the mouse atrium by possible activation of the NPY1 receptor.
Neuropeptide Y (NPY) causes various central and peripheral actions through activation of G-protein-coupled NPY receptors. Although a species-dependent difference in cardiac actions of NPY has been reported, the responses to NPY have not been examined in mice, widely used experimental animals. This study aimed to clarify the responses to NPY and the receptor subtype involved in the responses in mouse atrium. Neuropeptide Y caused negative inotropic and negative chronotropic actions in spontaneous beating right atria. Negative inotropic actions were more marked than negative chronotropic actions. Therefore, negative inotropic actions were studied in detail for evaluation of the NPY-induced cardiac actions in mouse atrium. Neuropeptide Y-induced negative inotropic actions were not affected by atropine but were abolished in the atria from pertussis toxin-treated mice. In isolated atrial preparations from reserpine-treated mice, NPY-induced negative inotropic actions were significantly attenuated. [Leu31, Pro34]-NPY, but not peptide YY, was effective in decreasing spontaneous contraction in atrial preparations. Although Y1 , Y2 , Y4 and Y5 receptor mRNAs were expressed almost equally in the brain, NPY1 receptor mRNA was dominantly expressed in the atrium. In conclusion, NPY caused negative inotropic and chronotropic actions through activation of the Y1 receptor in the mouse atrium. A high expression level of Y1 mRNA in the atrium suggests a functional role of NPY in the regulation of mouse cardiac contraction.


Octadentate hydroxypyridinonate (HOPO) ligands for plutonium (i.v.): pharmacokinetics and oral efficacy.
Linear octadentate spermine based 3,4,3-LI(1,2-HOPO) and the mixed ligand, 3,4,3-LI(1,2-Me-3,2-HOPO), are the most effective agents for decorporation of Pu prepared so far; they are effective at low dosage, orally active, and of low toxicity at effective injected dosage. Their pharmacological properties are favourable for in vivo Pu chelation--penetration of extracellular water, useful residence in the circulation, substantial hepato-biliary excretion, low but useful GI absorption, and transitory residence in the kidneys. Reductions of body Pu were significant, compared with controls, when oral administration to normally fed mice (30 or 100 micromol kg(-1)) was delayed as long as 24 h after i.v. Pu injection. The HOPO ligands (10-100 micromol kg(-1)) or CaNa3-DTPA (100 or 300 micromol kg(-1)) were given orally to normally fed mice starting at 4 h after an i.v. Pu injection and continued 5 d per week for 3 weeks. 3,4,3-LI(1,2-HOPO) (100 micromol kg(-1)) reduced Pu in skeleton, liver, and body, to 44 +/- 9, 18 +/- 8, and 38 +/- 7% of controls, respectively, reductions significantly greater than with the mixed HOPO ligand or with three times more CaNa3-DTPA.


Contemporary concepts on periodontal complications from prosthetic and restorative therapies.
The clinical outcome of every prosthetic and restorative procedure depends on the maintenance of a healthy periodontium. It is, therefore, important that the prosthodontist and restorative dentist cause no harm or permanent damage to the underlying hard and soft tissues when performing clinical procedures necessary to carry out the planned treatment. Several factors involved in these procedures have been described to have an impact on gingival health. For the present article, a selection of four of these factors are presented with the goal of evaluating the current trends and their influence on periodontal structures: (1) tooth preparation configuration and apical extension, (2) gingival tissue sulcular expansion/retraction, (3) prosthetic contours, and (4) prosthesis marginal adaptation and the consequences of excess cement remnants. Based on the available scientific evidence and clinical experience, recommendations for the practitioner are given.


Viscothionin purified from mistletoe (Viscum album var. coloratum Ohwi) induces insulin secretion from pancreatic beta cells.
Mistletoe (Viscum album), an evergreen parasitic plant, has been widely used as an oriental phytomedicine to treat diabetes mellitus. However, it is unknown which mistletoe constituent exerts the beneficial effect against the disease. In this study, we examined the hypoglycemic activity of mistletoe and investigated whether the polypeptide viscothionin, purified from mistletoe, was responsible for the activity. Mistletoe extracts were prepared by heating mistletoe powder made of leaves and twigs in water for 3, 6, 9, and 12 h. Rat insulinoma RINm5F cells were used to test the cytotoxicity of the extracts and their effects on the secretion of insulin and its precursor, C-peptide. The inhibitory effects of a mistletoe extract on glucose absorption were measured using an α-glucosidase inhibition assay. To determine the component of mistletoe responsible for the observed effects, the mistletoe extract was precipitated with ethanol or hydrolyzed with a protease for further testing. A potential active constituent of mistletoe was isolated by chromatography and molecular weight cut-off fractionation, and its ability to induce insulin secretion was investigated. A 12-h heat-treated mistletoe extract, showing no cytotoxicity, significantly increased the secretion of insulin and C-peptide by RINm5F cells and enhanced the expression of glucose transporter type 4 (GLUT-4), insulin receptor substrate 1 (IRS-1), and protein kinase B (also known as AKT) in differentiated C2C12 cells. The extract also inhibited α-glucosidase activity. After ethanol precipitation, the extract showed much stronger effects on insulin- and C-peptide-secreting activities of cells, whereas the enzyme-hydrolyzed extract was less effective than the original extract, suggesting that the effect was mediated by a proteinaceous constituent of mistletoe. Subsequent analysis showed that viscothionin, a heat-stable 6-kDa polypeptide isolated from mistletoe, increased the level of insulin secretion by more than 20-fold compared to that induced by the extract. Our study indicates that the hypoglycemic effect of mistletoe is mediated by its insulinotropic action and α-glucosidase inhibitory activity, and the effect is due to viscothionin, one of the major bioactive constituents of mistletoe.


Effects of exposure to pups on maternal behaviour, sexual behaviour and serum prolactin concentrations in male rats.
Male rats showed maternal behaviour within 72 h after the onset of continuous exposure to newborn rat pups. The latency of the behavioural response could be reduced by daily treatment with the dopamine receptor antagonist domperidone (2 X 2.5 mg/rat), which increased serum prolactin concentrations (241.4 +/- 26.5 (S.E.M.) micrograms/l) above those of vehicle-treated males exposed to pups (25.3 +/- 11.7 micrograms/l). Male rats did not respond to exposure to pups by secreting prolactin; keeping endogenous prolactin concentrations at a minimum (2.8 +/- 0.1 micrograms/l) by daily treatment with the dopamine receptor agonist bromocriptine (0.5 mg/rat) did not affect the behavioural response of male rats to newborn pups. Neither exposure to pups nor the modest hyperprolactinaemia induced by daily domperidone treatment affected the display of male sexual behaviour by male rats.


Effect of zinc on the activity of Cu/Zn superoxide dismutase and lipid profile in Wistar rats.
The aim of the present study was to analyze the effect of zinc on the activity of Cu/ZnSOD, lipid profile and arterial blood pressure in male Wistar rats. The study included 53 male Wistar rats with basal weight 190-210 g. The animals were divided into three groups and put on diets with different zinc content. Group I animals (G1, n = 18) were on a diet with zinc content 52 mg/kg, group II animals (G2, n = 18) were on a diet with zinc content 155 mg/kg corresponding to standard food and group III animals (G3, n = 17) received zinc supplementation (236 mg/kg diet). The activity of Cu/ZnSOD was measured in erythrocytes with RANSOD reactive (RANDOX). Zinc content in the laboratory chow and serum concentration of zinc and copper were analyzed by direct flame atomic-absorption spectrophotometry. Lipid profile was determined with reactives of ABX (France). Arterial blood pressure was measured on the rat's tail by an indirect method without anesthesia. Statistically significant decrease (p < 0.05) was found in the activity of Cu/ZnSOD in G1 animals (1993.51 +/- 303.01) compared with G2 animals (2307.07 +/- 240.23). There was a statistically significant increase (p < 0.05) of serum LDL in G3 (1.52 +/- 0.21) compared with G1 animals (1.09 +/- 0.27) and statistically significant increase in the serum triglycerides in G1 animals (1.19 +/- 0.22) compared with G3 animals (0.75 +/- 0.17). The results indicate that the activity of Cu/ZnSOD changes in relation to zinc diet and this correlates with the change in the arterial blood pressure. Lipid variables also are influenced and zinc supplementation leads to increase in the serum LDL and decrease in the serum triglycerides in Wistar rats.


Lorazepam treatment of psychogenic catatonia: an update.
Six papers have reported the efficacy of lorazepam in alleviating catatonic symptoms that have psychogenic causes. The authors report five new cases of catatonia; three patients responded favorably and two failed to respond to lorazepam. Investigation of the nonresponders revealed the presence of pernicious anemia in one and postpartum psychosis in the other. These findings demonstrate that lorazepam has an important role in the treatment of catatonic symptoms. Its effects appear to be specific for psychogenic catatonic states and for conditions in which biogenic amines, specifically dopamine and gamma-aminobutyric acid, play a part. The authors stress intramuscular administration of lorazepam for patients in catatonic states because this route provides the psychiatrist with immediate results that assist with early diagnosis and treatment.


[Contribution to facial spasm (author's transl)].
Clinical, electromyographic, neurographic, and nystagmographic results of 20 cases of facial spasm are reported. The syndrome is discussed with reference to parabiosis of the facial nerve and the "ephapse" theory, the localization of facial nerve lesions, and possible etiologic factors of parabiotic changes. For the pathogenesis chronic and subclinical preimpairments of facial nerve axons are postulated as causing, after subsequent additional affections, an "ephaptic" transfer to neighboring fibers. Therapeutic possibilities are discussed.


Patients' views of nurses' competence.
This study examines, from the patients' perspective, what is meant by competent nursing and how, with this perspective in mind, patients would view the prospect of assessing the competence of nurses. There is a little empirical research that clarifies professional competence from the patient's perspective. Nursing curricula in the UK have shifted attention to 'competencies' as the outcome of nurse education and, in an era of patient involvement, their views are important to investigate. The study utilises a grounded theory approach. Data were collected in Central Scotland between 2001 and 2003. Twenty-seven patients participated. Data were analysed, in keeping with the grounded theory tradition, utilising the constant comparative method. Patients described the foundation of competent nursing practice as technical care and nursing knowledge. Patients assume that technical care is competent as safe guards are considered to be in place to protect patients. When technical competence is assumed, interpersonal attributes become the most important indicator of the quality of nursing care. The results of this study highlight uncertainty about whether patients feel able to assess the competence of nurses. The results of this study may have implications for nurses internationally when trying to involve patients in the assessment of nurses.


Focal adhesion kinase overexpression enhances ras-dependent integrin signaling to ERK2/mitogen-activated protein kinase through interactions with and activation of c-Src.
Cell adhesion to extracellular matrix proteins such as fibronectin (FN) triggers a number of intracellular signaling events including the increased tyrosine phosphorylation of the cytoplasmic focal adhesion protein-tyrosine kinase (PTK) and also the stimulation of the mitogen-activated protein kinase ERK2. Focal adhesion kinase (FAK) associates with integrin receptors, and FN-stimulated phosphorylation of FAK at Tyr-397 and Tyr-925 promotes the binding of Src family PTKs and Grb2, respectively. To investigate the mechanisms by which FAK, c-Src, and Grb2 function in FN-stimulated signaling events to ERK2, we expressed wild type and mutant forms of FAK in human 293 epithelial cells by transient transfection. FAK overexpression enhanced FN-stimulated activation of ERK2 approximately 4-fold. This was blocked by co-expression of the dominant negative Asn-17 mutant Ras, indicating that FN stimulation of ERK2 was Ras-dependent. FN-stimulated c-Src PTK activity was enhanced by wild type FAK expression, whereas FN-stimulated activation of ERK2 was blocked by expression of the c-Src binding site Phe-397 mutant of FAK. Expression of the Grb2 binding site Phe-925 mutant of FAK enhanced activation of ERK2, whereas a kinase-inactive Arg-454 mutant FAK did not. Expression of wild type and Phe-925 FAK, but not Phe-397 FAK, enhanced p130(Cas) association with FAK, Shc tyrosine phosphorylation, and Grb2 binding to Shc after FN stimulation. FN-induced Grb2-Shc association is another pathway leading to activation of ERK2 via Ras. The inhibitory effects of Tyr-397 FAK expression show that FAK-mediated association and activation of c-Src is essential for maximal signaling to ERK2. Moreover, multiple signaling pathways are activated upon the formation of an FAK.c-Src complex, and several of these can lead to Ras-dependent ERK2 mitogen-activated protein kinase activation.


Absence labels: How does information about production practices impact consumer demand?
Absence labels promote the absence of a particular ingredient or production practice. Consumers usually perceive organic labels as an umbrella absence label for a variety of ingredients and production practices. Such organic labels often use similar language but are based on different certification requirements. For example, both organic wine and wine made with organic grapes are available to U.S. consumers, but little is known about consumer preferences for such labeled products when information about the certification standards is available. Moreover, while absence labels, which advertise the absence of certain attributes or practices, are prevalent on the market, little is known about how information on conventional production practices impacts consumer behavior. Using an artefactual experiment with 128 adult non-student participants, we investigate consumer demand for conventional wine, organic wine, and wine made with organic grapes when information about production standards is provided to participants with and without details regarding conventional winemaking practices. We find that while both organic labels carry a significant and very similar willingness-to-pay (WTP) premium, information about certification standards and conventional wine making practices can reduce WTP for all wines. Providing information about the two organic certification standards reduces consumer WTP for both absence labeled and conventional wine categories. This effect largely disappears for organic wine, but not wine made with organic grapes, when information about conventional wine-making practices is also provided.


MicroRNA expression profiling in patients with hepatocellular carcinoma of familial aggregation and hepatitis B virus infection.
Numerous studies have suggested that microRNAs (miRNAs) potently affect hepatocarcinogenesis. However, the miRNA expression profiling in patients with hepatocellular carcinoma (HCC) of familial aggregation and hepatitis B virus (HBV) infection has not been elucidated. In the present study, the plasma miRNA expression profiles of 3 patients with HCC with familial aggregation of HCC and HBV infection and 1 healthy volunteer were examined by microarray analysis, in order to identify relevant miRNAs involved in the pathogenesis of HCC with familial aggregation and HBV infection. The results indicated that 26 miRNAs exhibited a ≥20-fold increase or decrease in the plasma of patients with HCC, compared with the healthy control (24 upregulated and 2 downregulated). Among these altered miRNAs, 15 of them have been reported in HCC. The other 11 miRNAs have never been reported in HCC. These differentially-expressed miRNAs may be potential molecular markers for HCC pathogenesis and development.


Long-term physical functioning and its association with somatic comorbidity and comorbid depression in patients with established rheumatoid arthritis: a longitudinal study.
To describe long-term physical functioning and its association with somatic comorbidity and comorbid depression in patients with established rheumatoid arthritis (RA). Longitudinal data over a period of 11 years were collected from 882 patients with RA at study inclusion. Patient-reported outcomes were collected in 1997, 1998, 1999, 2002, and 2008. Physical functioning was measured with the Health Assessment Questionnaire and the physical component summary score of the Short Form 36 health survey. Somatic comorbidity was measured by a questionnaire including 12 chronic diseases. Comorbid depression was measured with the Center for Epidemiologic Studies Depression Scale. We distinguished 4 groups of patients based on comorbidity at baseline. Seventy-two percent of the patients at baseline were women. The mean ± SD age was 59.3 ± 14.8 years and the median disease duration was 5.0 years (interquartile range 2.0-14.0 years). For the total group of patients with RA, physical functioning improved over time. Patients with somatic comorbidity, comorbid depression, or both demonstrated worse physical functioning than patients without comorbidity at all data collection points. Both groups with comorbid depression had the lowest scores. Only patients with both somatic comorbidity and comorbid depression showed significantly less improvement in physical functioning over time. Both somatic comorbidity and comorbid depression were negatively associated with physical functioning during an 11-year followup period. Furthermore, their combination seems to be especially detrimental to physical functioning over time. These results emphasize the need to take somatic comorbidity and comorbid depression into account in the screening and treatment of patients with RA.


Mitochondrial iron supply is required for the developmental pulse of ecdysone biosynthesis that initiates metamorphosis in Drosophila melanogaster.
Synthesis of ecdysone, the key hormone that signals the termination of larval growth and the initiation of metamorphosis in insects, is carried out in the prothoracic gland by an array of iron-containing cytochrome P450s, encoded by the halloween genes. Interference, either with iron-sulfur cluster biogenesis in the prothoracic gland or with the ferredoxins that supply electrons for steroidogenesis, causes a block in ecdysone synthesis and developmental arrest in the third instar larval stage. Here we show that mutants in Drosophila mitoferrin (dmfrn), the gene encoding a mitochondrial carrier protein implicated in mitochondrial iron import, fail to grow and initiate metamorphosis under dietary iron depletion or when ferritin function is partially compromised. In mutant dmfrn larvae reared under iron replete conditions, the expression of halloween genes is increased and 20-hydroxyecdysone (20E), the active form of ecdysone, is synthesized. In contrast, addition of an iron chelator to the diet of mutant dmfrn larvae disrupts 20E synthesis. Dietary addition of 20E has little effect on the growth defects, but enables approximately one-third of the iron-deprived dmfrn larvae to successfully turn into pupae and, in a smaller percentage, into adults. This partial rescue is not observed with dietary supply of ecdysone's precursor 7-dehydrocholesterol, a precursor in the ecdysone biosynthetic pathway. The findings reported here support the notion that a physiological supply of mitochondrial iron for the synthesis of iron-sulfur clusters and heme is required in the prothoracic glands of insect larvae for steroidogenesis. Furthermore, mitochondrial iron is also essential for normal larval growth.


Assessing the synergy between cholinomimetics and memantine as augmentation therapy in cognitive impairment in schizophrenia. A virtual human patient trial using quantitative systems pharmacology.
While many drug discovery research programs aim to develop highly selective clinical candidates, their clinical success is limited because of the complex non-linear interactions of human brain neuronal circuits. Therefore, a rational approach for identifying appropriate synergistic multipharmacology and validating optimal target combinations is desperately needed. A mechanism-based Quantitative Systems Pharmacology (QSP) computer-based modeling platform that combines biophysically realistic preclinical neurophysiology and neuropharmacology with clinical information is a possible solution. This paper reports the application of such a model for Cognitive Impairment In Schizophrenia (CIAS), where the cholinomimetics galantamine and donepezil are combined with memantine and with different antipsychotics and smoking in a virtual human patient experiment. The results suggest that cholinomimetics added to antipsychotics have a modest effect on cognition in CIAS in non-smoking patients with haloperidol and risperidone and to a lesser extent with olanzapine and aripiprazole. Smoking reduces the effect of cholinomimetics with aripiprazole and olanzapine, but enhances the effect in haloperidol and risperidone. Adding memantine to antipsychotics improves cognition except with quetiapine, an effect enhanced with smoking. Combining cholinomimetics, antipsychotics and memantine in general shows an additive effect, except for a negative interaction with aripiprazole and quetiapine and a synergistic effect with olanzapine and haloperidol in non-smokers and haloperidol in smokers. The complex interaction of cholinomimetics with memantine, antipsychotics and smoking can be quantitatively studied using mechanism-based advanced computer modeling. QSP modeling of virtual human patients can possibly generate useful insights on the non-linear interactions of multipharmacology drugs and support complex CNS R&D projects in cognition in search of synergistic polypharmacy.


Examination of CA1 Hippocampal DNA Methylation as a Mechanism for Closing of Estrogen's Critical Window.
There is a critical window for estrogen replacement therapy, beyond which estradiol (E2) fails to enhance cognition and N-methyl-D-aspartate (NMDA) receptor function, and E2-responsive transcription decreases. Much less attention has been given to the mechanism for closing of the critical window, which is thought to involve the decline in estrogen signaling cascades, possibly involving epigenetic mechanisms, including DNA methylation. This study investigated changes in DNA methylation in region CA1 of the hippocampus of ovariectomized female rats over the course of brain aging and in response to E2-treatment, using whole genome bisulfite sequencing. Differential methylation of CpG and non-CpG (CHG and CHH) sites and associated genes were characterized in aged controls (AC), middle-age controls (MC), and young controls (YC) and differential methylation in response to E2-treatment (T) was examined in each age group (AT-AC, MT-MC, and YT-YC). Possible candidate genes for the closing of the critical window were defined as those that were hypomethylated by E2-treatment in younger animals, but were unresponsive in aged animals. Gene ontology categories for possible critical window genes were linked to response to hormones (Adcyap1, Agtr2, Apob, Ahr, Andpro, Calm2, Cyp4a2, Htr1b, Nr3c2, Pitx2, Pth, Pdk4, Slc2a2, Tnc, and Wnt5a), including G-protein receptor signaling (Gpr22 and Rgs4). Other possible critical window genes were linked to glutamate synapses (Nedd4, Grm1, Grm7, and Grin3a). These results suggest that decreased E2 signaling with advanced age, and/or prolonged E2 deprivation, results in methylation of E2-responsive genes, including those involved in rapid E2 signaling, which may limit subsequent transcription.


DIPK2A promotes STX17- and VAMP7-mediated autophagosome-lysosome fusion by binding to VAMP7B.
Autophagosome and lysosome fusion is an important macroautophagy/autophagy process for cargo degradation, and SNARE proteins, including STX17, SNAP29, VAMP7 and VAMP8, are key players in this process. However, the manner in which this process is precisely regulated is poorly understood. Here, we show that VAMP7B, a SNARE domain-disrupted isoform of R-SNARE protein VAMP7, competes with SNARE domain functional isoform VAMP7A to bind to STX17 and inhibits autophagosome-lysosome fusion. Moreover, we show that DIPK2A, a late endosome- and lysosome-localized protein, binds to VAMP7B, which inhibits the interaction of VAMP7B with STX17 and enhances the binding of STX17 to VAMP7A, thus enhancing autophagosome-lysosome fusion. Furthermore, DIPK2A participates in autophagic degradation of mitochondria proteins and alleviates apoptosis. Thus, we reveal a new aspect of autophagosome-lysosome fusion in which different isoforms of VAMP7 compete with STX17 and their regulation by DIPK2A.Abbreviations: DIPK2A: divergent protein kinase domain 2A; EEA1: early endosome antigen 1; GOLGA2: golgin A2; LAMP1: lysosomal associated membrane protein 1; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MFN2: mitofusin 2; MT-CO2: mitochondrially encoded cytochrome c oxidase II; PARP1: poly(ADP-ribose) polymerase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; RAB5A: RAB5A, member RAS oncogene family; RAB7A: RAB7A, member RAS oncogene family; REEP: receptor accessory protein; RTN4: reticulon 4; SNARE: SNAP receptor; SQSTM1/p62: sequestosome 1; STX17: syntaxin 17; TOMM20: translocase of outer mitochondrial membrane 20; VAMP7: vesicle associated membrane protein 7; VAMP8: vesicle associated membrane protein 8.


Comparison of morphine and tramadol by patient-controlled analgesia for postoperative analgesia after tonsillectomy in children.
Tramadol is an alternative to other opioids for postoperative pain management. This prospective, randomized, double-blind study was designed to compare the analgesic efficacy of patient-controlled tramadol with patient-controlled morphine for postoperative pain after tonsillectomy in children. Sixty patients were allocated randomly to receive a patient-controlled analgesia (PCA) with either tramadol (T) or morphine (M), in a double-blind randomized study. When surgery was completed and hemostasis achieved, a standardized loading dose (0.1 mg.kg(-1) in group M, or 1 mg.kg(-1) in group T) was given. Thereafter, the children helped themselves to bolus doses (morphine (0.02 mg.kg(-1)) or tramadol (0.2 mg.kg(-1)) with lock-out times of 10 min without time limit via a PCA device. Scores for pain, sedation, nausea, and the bolus and total PCA doses, hemodynamic parameters and side effects were recorded at 5, 15, 30 min and 1, 2, 4, 6 and 24 h during PCA administration. Pain scores decreased significantly with time in both groups (P < 0.05), but were lower in group M than in group T at 1, 2 and 4 h (P < 0.05). Sedation scores increased with time in both groups (P < 0.05). However there were no significant differences in sedation scores between two groups at any study period, but nausea scores were higher in M group at 4, 6 and 24 h (P < 0.05). Intravenous patient-controlled tramadol is an alternative to patient-controlled morphine for postoperative pain relief in children after tonsillectomy. Morphine gave better postoperative pain relief, but was associated with a higher incidence of nausea than tramadol.


[Use of psychological pain-control technics in psychiatry].
In recent years the initial attempts at algotherapy employing the predominating forms, such as medicinal treatment, electrotherapy, and operative treatment, have greatly improved the care of patients suffering pain. Psychological pain control techniques are a further feasible means of treatment. They include cognitive and behavioral intervention techniques in part already well known that can accompany and enhance traditional forms of anodyne therapy. By way of example, the concept of "pain inoculation" (Bullinger & Turk, 1982) is described in its sequence of phases. Methods of application in clinical practice are referred to.


Multidrug resistant transgenic mice as a novel pharmacologic tool.
Multidrug resistance resulting from expression of an energy-dependent drug efflux pump encoded by the human MDR1 gene is a major impediment to effective cancer therapy. Pharmacologic intervention aimed at inhibiting this multidrug transporter should improve existing chemotherapy of human cancer, but drug development has been delayed by the difficulty and expense of developing valid animal models. Using recombinant DNA technology, a transgenic mouse has been engineered whose bone marrow is protected from the toxic effects of chemotherapy by expression of the MDR1 gene. This animal system allows the rapid screening of drugs which inhibit the multidrug transporter and heralds a new era of using transgenic animals for pharmacologic screening.


[Multidisciplinary approach of the obese child to the dietary residency of "Clairs Vallons"].
The pediatric obesity has become a real problem for the public health. One estimates that about 16% of the Belgian pediatric population and up to 33% of the Americans are concerned by this problematic. 70% of the teenagers will remain obese once adult if no treatment is proposed during the childhood. Because of that evolution, some journalists wrote: "that the old continent would be able to catch up with the new world in the next ten years". The malnutrition is not however the only factor at the origin of the obesity. The sedentary lifestyle (lack of exercise, TV, Internet, video games) the domestic organization, the "various emotional stress "are to be blamed. It is without taking into consideration the paradox of our consumption society that while extolling the cult of the slim, young and dynamic body, etc., pushes us to consume more, encouraging in some social and cultural surroundings to go for the immediate pleasure to the detriment of the knowledge - understanding - of our own body. Which places the obese child in an existential paradox. If on top of it there is a domestic predisposition to the plumpness, the kilograms in excess are threatening the unsecured child and new sufferings stand out on the horizon : relational unrests, isolation, social dismissal, reduction of the esteem of selfesteem as well as lack of confidence, less freedom, depression, etc. Not only are they victims of mockeries, aggressiveness and exclusion, the children put their health in danger. On those children we can notice an increase of the impact of cardiovascular pathologies, diabetes, cancers of the intestines, etc. In "Clairs Vallons" we put the hypothesis that the children and the teenagers who come here in custody could suffer from a lack of presence as well as people listening to them and that therefore to would search for comfort in eating. We consider that all interventions based solely on the interdiction of the symptom have no result, causes more suffering and a displacement of the symptom. The therapeutic work to the Dietary Residency of "Clairs Vallons" consists therefore in a global approach of the child within a multidisciplinary team (pediatrician, dietitian, psychologist, physiotherapist, social assistant, orthofenist, educator and teacher) all united around the concept "to eat happy".


Effect of a zirconium tungstate filler on the cure behavior of a cyanate ester resin.
In this work, the effect of a negative thermal expansion zirconium tungstate (ZrW2O8) filler on the cure behavior of a unique low-viscosity bisphenol E cyanate ester (BECy) is characterized by differential scanning calorimetry. The cure rate of BECy is found to increase upon the incorporation of ZrW2O8 particles, and the catalytic effect increases with increasing filler loading. The catalytic effect is primarily attributed to the presence and nature of hydroxyl groups on the ZrW2O8 particle surface. In comparison with BECy/ZrW2O8 composites of the same loading, silane-coated ZrW2O8 particles resulted in a higher value of the glass transition temperature (T(g)) and a delay in the onset of the cure. The ability of a phenomenological reaction model to describe the cure behavior of the composites is also examined.


Clear Cell Proliferations of the Skin: A Histopathologic Review.
Cutaneous clear cell proliferations encompass a heterogenous group of several primary cutaneous neoplasms and metastatic tumors with different histogenesis. Many of these clear cell proliferations may seem strikingly similar under the microscope resulting in challenging diagnosis. In many of these clear cell lesions, the reason for the clear or pale appearance of proliferating cells is unknown, whereas in other ones, this clear cell appearance is due to intracytoplasmic accumulation of glycogen, mucin, or lipid. Artifacts of tissue processing and degenerative phenomenon may also be responsible for the clear cell appearance of proliferating cells. Awareness of the histopathologic findings as well as histochemical and immunohistochemical techniques are crucial to the accurate diagnosis. This review details the histopathologic features of clear cell cutaneous proliferations, classifying them according their type of differentiation and paying special attention to the histopathologic differential diagnosis among them.


[Randomized controlled trial on effect of Tuina for treatment of sub-health people of somatic pain].
To evaluate the clinical effect and safety of Tuina for treatment of somatic pain of sub-health. A randomized, double-blind and blank parallel controlled trial was done. The experiment group was treated with Tuina and the control group lied down for rest, 45 minutes each time, twice each week for three weeks. Tuina treatment could improve more on sensory, affective, evaluation, pain rating index and extant pain intensity of the pain index, and score of subjective sensation of life quality and health status together with physiology and psychology field of life quality. Massage is an effective therapy for treatment of somatic pain of sub-health without adverse reactions and it should be generalized to application.


Research progress in physiological effects of resistant substances of Urtica dioica L. on animal performance and feed conversion.
Several members of family Urticaceae are mainly found in the temperate and subtropical zones of the Northern Hemisphere and are important medicinal plants. Among them, Urtica dioica L. (Urticaceae) is an annual or perennial herb that has been used for feeding and medicinal purposes since long time and is the most exploited species of Urticaceae. Recently, it has received attention to be used as animal feed, as its fresh leaves fed to animals in moderate, dried, and other forms. This review details the advantages of U. dioica as an alternative feed in terms of germplasm specificity, nutritional composition, and feed application status. Its roots, stems, leaves, and seeds are rich in active ingredients. It has also been found to have anticancer effects through antioxidant action and promotion of apoptosis of cancer cells. In shady conditions, U. dioica is highly adaptable while under stressful conditions of drought; it also reduces light absorption and ensures carbon assimilation through light energy conversion efficiency. Therefore, it can be added to animal diets as a suitable feed to reduce costs and improve economic efficiency. This paper investigates the feasibility of using U. dioica as a feed and systematically presents the progress of research and exploitation of U. dioica.


Plant growth-promoting actinobacteria: a new strategy for enhancing sustainable production and protection of grain legumes.
Grain legumes are a cost-effective alternative for the animal protein in improving the diets of the poor in South-East Asia and Africa. Legumes, through symbiotic nitrogen fixation, meet a major part of their own N demand and partially benefit the following crops of the system by enriching soil. In realization of this sustainability advantage and to promote pulse production, United Nations had declared 2016 as the "International Year of pulses". Grain legumes are frequently subjected to both abiotic and biotic stresses resulting in severe yield losses. Global yields of legumes have been stagnant for the past five decades in spite of adopting various conventional and molecular breeding approaches. Furthermore, the increasing costs and negative effects of pesticides and fertilizers for crop production necessitate the use of biological options of crop production and protection. The use of plant growth-promoting (PGP) bacteria for improving soil and plant health has become one of the attractive strategies for developing sustainable agricultural systems due to their eco-friendliness, low production cost and minimizing consumption of non-renewable resources. This review emphasizes on how the PGP actinobacteria and their metabolites can be used effectively in enhancing the yield and controlling the pests and pathogens of grain legumes.


Clinical characteristics of COPD patients with tidal expiratory flow limitation.
We have used impulse oscillometry to identify COPD patients with tidal expiratory flow limitation (EFL), which is a measurement related to small airway disease. We report that 37.4% of COPD patients had EFL; these patients had multiple clinical characteristics of more severe disease including lower forced expiratory volume in 1 second values, greater hyperinflation, reduced exercise performance, and increased small airway impairment. We highlight that EFL can be used to identify a subgroup of COPD patients with distinct characteristics associated with small airway disease.


Biosynthesis, purification, and substrate specificity of severe acute respiratory syndrome coronavirus 3C-like proteinase.
The 3C-like proteinase of severe acute respiratory syndrome (SARS) coronavirus has been proposed to be a key target for structural-based drug design against SARS. In order to understand the active form and the substrate specificity of the enzyme, we have cloned, expressed, and purified SARS 3C-like proteinase. Analytic gel filtration shows a mixture of monomer and dimer at a protein concentration of 4 mg/ml and mostly monomer at 0.2 mg/ml, which correspond to the concentration used in the enzyme assays. The linear decrease of the enzymatic-specific activity with the decrease of enzyme concentration revealed that only the dimeric form is active and the dimeric interface could be targeted for structural-based drug design against SARS 3C-like proteinase. By using a high pressure liquid chromatography assay, SARS 3C-like proteinase was shown to cut the 11 peptides covering all of the 11 cleavage sites on the viral polyprotein with different efficiency. The two peptides corresponding to the two self-cleavage sites are the two with highest cleavage efficiency, whereas peptides with non-canonical residues at P2 or P1' positions react slower. The P2 position of the substrates seems to favor large hydrophobic residues. Secondary structure studies for the peptide substrates revealed that substrates with more beta-sheetlike structure tend to react fast. This study provides a basic understanding of the enzyme catalysis and a full substrate specificity spectrum for SARS 3C-like proteinase, which are helpful for structural-based inhibitor design against SARS and other coronavirus.


Anopheles barbirostris/campestris as a probable vector of malaria in Aranyaprathet, Sa Kaeo Province.
As a result of dramatic increase in malaria cases in Sa Kaeo Province from 666 cases in 1995 to 4,381 in 1997, a brief entomological study was carried out during January 1998 to December, 1999 in Pa Rai subdistrict where most malaria cases were reported. Of fourteen species of mosquitos found, only Anopheles barbirostris group was the most abundant species throughout the year. Adult identification was not able to confirm species within An. barbirostris group, particularly between An. barbirostris and An. campestris because of morphological resemblance. Therefore, the barbirostris group captured in this study is reported to be either An. barbirostris or An. campestris. The seasonal prevalence of barbirostris/campestris was bimodal in distribution (September and November) and coincided well with malaria occurrence in this area. Human landing collections revealed high adult densities with 20 bites/person-night for mean indoor density and 53.5 bites/person-night for mean outdoor density. The biting peak was during 21.00-24.00 hours. Among 223 barbirostris/campestris dissected for oocysts and sporozoites only one gut from the outdoor collection in November was infected with oocysts. There were no sporozoites detected in salivary glands of all mosquitos collected. This appears to indicate that in the absence of major vectors local species may serve as potential transmitters of malaria in Thailand.


Allergic diseases and climate changes: our experience and an update.
Recent research has shown that there are many effects of climate change on aeroallergens and thus allergic diseases in humans. It is not easy to evaluate the impact of climate change and air pollution on the prevalence of allergic diseases. The present study is devoted to decipher the possible relationships between climatic changes and allergic diseases, and in particular with atopic dermatitis (AD). To evaluate the aeroallergens effects on AD, we submitted to an allergological study protocol 59 children patients with AD to study the interaction between aeroallergens-atopy patch test (APT) and skin prick test (SPT). The same tests were performed on to the same patients after 24 months to assess the time trend. We found a high prevalence of house dust mites and grasses pollen APT positivity in AD's and in respiratory patients and we also found an increase in positive results in the same patients after 24 months. However, we observed a variation in the control group, in which in earlier tests all patients had negative results but after 24 months we found some positivity. We found a correlation between APT and SPT in AD and we observed a concordance between APT results and the atopy score index, underlying the triggering role of these aereoallergens in the atopic patient's skin reactivity.


Milk urea nitrogen concentration is higher in Brown Swiss than in Holstein dairy cows despite identical feeding.
Milk urea nitrogen (MUN) content is closely related to blood urea nitrogen (BUN) concentration and reflects the balance of dietary crude protein and energy supply for ruminal microbial metabolism. The present study investigated whether the higher MUN content in Brown Swiss (BSW) compared with Holstein (HOL) cows is related to milk production and feeding conditions. Therefore, we evaluated test-day records of three consecutive official milk recordings from 86 BSW and 200 HOL cows kept on the same farm under identical feeding and management conditions. In addition, the relationships between BUN and MUN assessed either by an enzymatic method or by mid-infrared spectroscopy were analysed. For the second objective, milk and blood samples (1,112 samples each) were collected in parallel from day 5 until day 150 of lactation from 141 dairy cows housed at different farms. Concentrations of MUN determined either enzymatically (MUNENZ ) or by Fourier transform infrared spectroscopy (FTIR; MUNIR ) were regressed on the BUN concentrations of the concomitantly obtained blood samples. Both MUNIR and MUNENZ were well correlated with BUN (r = .93 and .89 respectively). Concentration of MUN was higher in BSW compared with HOL independently of lactational stage or parity number (p < .0001). Protein and fat content were higher in BSW than in HOL (p < .05). Primiparous cows had lower milk yield and ECM (p < .001 for BSW, p < .0001 for HOL) than multiparous in both breeds. Multiparous BSW had a similar milk production than primiparous HOL (p = .13). In conclusion, BSW cows have higher MUN than HOL when kept under identical feeding and management conditions. The higher MUN in BSW compared with HOL cows is not related to milk production and therefore rather genetically determined.


Immediate flow-diversion characteristics of a novel primarily bioresorbable flow-diverting stent.
Flow-diverting stents with a resorbable component have significant theoretical benefits over full metal stents, although currently there are none in clinical use. In this study, the authors sought to determine the immediate flow-diversion characteristics of a novel primarily bioresorbable flow-diverting stent. Bioresorbable stents were deployed into glass tube models to determine porosity and pore density. In vitro flow diversion behavior was evaluated using high frame rate angiography under pulsatile flow conditions in a patient-specific silicone aneurysm model treated with the resorbable stent as well as the Surpass Evolve stent. In vivo flow diversion was characterized by deployment into 20 rabbit saccular aneurysm models, and grading was based on the O'Kelly-Marotta scale and the 4F-flow diversion predictive score. Porosities and pore densities of the bioresorbable stent were in the flow-diverting range for all target vessel diameters. Quantified results of immediate angiography after placement of the bioresorbable stent into a silicone aneurysm model demonstrated greater flow diversion compared to the Evolve stent. Bioresorbable stent placement in saccular aneurysm models resulted in an immediate O'Kelly-Marotta grade of A3 or better and a 4F-flow diversion predictive score of 4 or better in all cases. The bioresorbable stent has immediate flow-diversion characteristics that are comparable to commercially available metal stents. Longer-term studies are underway to determine the ability of the resorbable fibers to act as a neointimal scaffold and result in long-term aneurysm occlusion.


Observation of Anisotropic Thermal Expansion and the Jahn-Teller Effect in Double Perovskites Sr2-xLaxCoNbO6 Using Neutron Diffraction.
We use temperature dependent neutron powder diffraction (NPD) to investigate the structural changes and magnetic interactions in double perovskite Sr2-xLaxCoNbO6 (x = 0.4 and 0.6). A structural phase transition from tetragonal (I4/m) to monoclinic (P21/n) is observed between x = 0.4 and 0.6 samples. Interestingly, the temperature evolution of the unit cell parameters follows the Grüneisen approximation, and the analysis suggests an isotropic thermal expansion in the case of the x = 0.4 sample, whereas the x = 0.6 sample shows the anisotropy where the thermal expansion along the c-axis significantly deviates from the Grüneisen function. We observe the z-out Jahn-Teller distortion in the CoO6 and consequently z-in distortion in the adjacent NbO6 octahedra. With an increase in the La substitution, a decrease in the degree of octahedral distortion is evident from the significant reduction in the local distortion parameter Δ around the B-site atoms.


De Novo Design of a Highly Stable Ovoid TIM Barrel: Unlocking Pocket Shape towards Functional Design.
The ability to finely control the structure of protein folds is an important prerequisite to functional protein design. The TIM barrel fold is an important target for these efforts as it is highly enriched for diverse functions in nature. Although a TIM barrel protein has been designed de novo, the ability to finely alter the curvature of the central beta barrel and the overall architecture of the fold remains elusive, limiting its utility for functional design. Here, we report the de novo design of a TIM barrel with ovoid (twofold) symmetry, drawing inspiration from natural beta and TIM barrels with ovoid curvature. We use an autoregressive backbone sampling strategy to implement our hypothesis for elongated barrel curvature, followed by an iterative enrichment sequence design protocol to obtain sequences which yield a high proportion of successfully folding designs. Designed sequences are highly stable and fold to the designed barrel curvature as determined by a 2.1 Å resolution crystal structure. The designs show robustness to drastic mutations, retaining high melting temperatures even when multiple charged residues are buried in the hydrophobic core or when the hydrophobic core is ablated to alanine. As a scaffold with a greater capacity for hosting diverse hydrogen bonding networks and installation of binding pockets or active sites, the ovoid TIM barrel represents a major step towards the de novo design of functional TIM barrels.


Comparative study of the quality characteristics of defatted soy flour treated by supercritical carbon dioxide and organic solvent.
Defatted soy flour is a potential source of food protein, amino acids, ash and isoflavones. The supercritical carbon dioxide (SC-CO2) and a traditional organic solvent extraction methods were used to remove fat from soy flour, and the quality characteristics of a control soy flour (CSF), defatted soy flour by SC-CO2 (DSFSC-CO2) and defatted soy flour by an organic solvent (DSF-OS) were compared. The SC-CO2 process was carried out at a constant temperature of 45 °C, and a pressure of 40 MPa for 3 h with a CO2 flow rate of 30 g/min. The DSFSC-CO2 had significantly higher protein, ash, and amino acids content than CSF and DSF-OS. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis demonstrated that CSF and DSFSC-CO2 had protein bands of similar intensity and area that indicated no denaturation of protein, whereas DSF-OS showed diffuse bands or no bands due to protein denaturation. In addition to higher nutritional value and protein contents, DSFSC-CO2 showed superior functional properties in terms of total soluble solids content, water and oil absorption, emulsifying and foaming capacity. The SC-CO2 method offers a nutritionally and environmentally friendly alternative extraction processing approach for the removal of oil from high-protein food sources. It has a great potential for producing high-protein fat-free, and low-calorie content diet than the traditional organic solvent extraction method.


Phase II trial of 13-cis-retinoic acid plus interferon-alpha in recurrent head and neck cancer.
13-cis-retinoic acid (isotretinoin) and interferon-alpha have limited activity as single agents in advanced cancer. Preclinical data indicate that these agents have different mechanisms of action and, in combination have greater activity (that is, the ability to modulate growth and differentiation) in a number of malignant cell types than either agent alone. In clinical trials, the new biological regimen of 13-cis-retinoic acid and interferon-alpha was shown to have major activity in advanced squamous cell carcinoma of the skin and cervix. We conducted a phase II trial of this regimen in recurrent squamous cell carcinoma of the head and neck. Of the 21 evaluable patients, none had a complete response, and only one had a partial response (5%). Two patients had minor responses, four had stable disease, and 14 experienced disease progression. Five patients developed grade 3 toxic effects, including skin toxicity, fatigue, headache, and anorexia/weight loss. The median survival duration was 25.5 weeks (range, 4-95). The combination of 13-cis-retinoic acid and interferon-alpha at this dose and schedule is ineffective for the treatment of recurrent squamous cell carcinoma of the head and neck.


Laparoscopic greater omentum harvesting with split-thickness skin grafting for sternal wound dehiscence.
Sternal wound dehiscence is a serious complication occasionally requiring soft tissue coverage. The greater omentum typically has been used as a last resort because of the underlying morbidity from a laparotomy. We present a case in which a laparoscopically created omental flap with subsequent split-thickness skin grafting was used to correct a large soft tissue defect that occurred after sternal wound dehiscence developed. A nonambulatory 49-year-old man who underwent coronary artery bypass grafting developed sternal wound dehiscence. Because a large soft tissue defect developed after multiple debridements, soft tissue coverage was required. A laparoscopically harvested omental flap spared this man's upper extremity musculature and provided a soft tissue bed for split-thickness skin grafting. This case helps to establish the role of laparoscopically harvested omentum. If the results suggested by this case are confirmed in a large series, omental flaps should be considered as options of first choice in the management of sternal wound dehiscence.


Determining the electronic performance limitations in top-down-fabricated Si nanowires with mean widths down to 4 nm.
Silicon nanowires have been patterned with mean widths down to 4 nm using top-down lithography and dry etching. Performance-limiting scattering processes have been measured directly which provide new insight into the electronic conduction mechanisms within the nanowires. Results demonstrate a transition from 3-dimensional (3D) to 2D and then 1D as the nanowire mean widths are reduced from 12 to 4 nm. The importance of high quality surface passivation is demonstrated by a lack of significant donor deactivation, resulting in neutral impurity scattering ultimately limiting the electronic performance. The results indicate the important parameters requiring optimization when fabricating nanowires with atomic dimensions.


Gender preference and awareness regarding sex determination among antenatal mothers attending a medical college of eastern India.
There are many women "missing" due to an unfavourable sex ratio in India, which has strong patriarchal norms and a preference for sons. Female gender discrimination has been reported in health care, nutrition, education, and resource allocation due to man-made norms, religious beliefs, and recently by ultrasonography resulting in lowered sex ratio. The present study attempts to find out the level of awareness regarding sex determination and to explore preference of gender and factors associated among antenatal mothers attending a medical college in eastern India. Interviews were done by predesigned pretested proforma over 6 months. The data were analysed by SPSS 16.0 software for proportions with chi-squared tests and binary logistic regression analysis. Most women who were multigravida did not know about contraceptives; 1.8% of mothers knew the sex of the fetus in present pregnancy while another 34.7% expressed willingness; 13.6% knew of a place which could tell sex of the fetus beforehand; 55.6% expressed their preference of sex of the baby for present pregnancy while 50.6% of their husbands had gender preference. Gender preference was significantly high in subjects with: lower socioeconomic status (p=0.011); lower level of education of mother (p=0.047) and husband (p=0.0001); multigravida (p=0.002); presence of living children (p=0.0001); and husband having preference of sex of baby (p=0.0001). Parental education, socioeconomic background, and number of living issues were the main predictors for gender preference. Awareness regarding gender preference and related law and parental counselling to avoid gender preference with adoption of small family norm is recommended.


Detection of a broad range of class I and II Newcastle disease viruses using a multiplex real-time reverse transcription polymerase chain reaction assay.
Prompt detection of virulent strains of Newcastle disease virus (vNDV) using real-time reverse transcription polymerase chain reaction (RT-PCR) is challenging because of the broad genetic variability across 2 clades comprising 18 recognized genotypes. A large proportion of class I low virulence ND viruses recently identified in samples recovered from wild birds and from poultry in live bird markets are not detected by the validated real-time RT-PCR assay that targets the matrix gene (M-gene assay). This study describes the identification and sequencing of a conserved region from the polymerase gene of class I NDV and the design and evaluation of a real-time RT-PCR assay (L-TET assay) that identifies a broad range of NDV, demonstrates a 10-fold increase in sensitivity over a previously reported L-gene assay, and works in conjunction with the existing M-gene assay using the same protocol. The L-TET assay detects <or=1 fg of homologous transcribed RNA from genotypes 5, 7, and 8 of class I, and from class II genotype II in either single- or multiplex format. Differential detection of mixed class I and II viruses down to 100 fg is possible because L-TET uses an alternate fluorophore from the M-gene assay. The multiplexed assay is capable of detecting a broad range of class I and II ND viruses with <1 threshold cycle decrease in sensitivity compared to the single probe. A total of 140 class I (n = 108, genotypes 1-2 and 4-9) and class II (n = 32, genotypes I-VII) were correctly identified by both the single- and multiplex formats.


The microbes of the intestine: an introduction to their metabolic and signaling capabilities.
This article summarizes advances in the field of host-microbe interactions in the gut. The human gut is home to a complex community of microbes (the microbiota) that plays a critical role in host nutrient acquisition and metabolism, development of intestinal epithelial cells, and host immune system. Genetic background, nutritional status, and environmental factors influence the structure and function of the gut microbiota. Networks for cell-cell communication include microbes actively communicating with microbes of the same and other species; host cells recognizing and interacting with commensal versus pathogenic organisms; and microbes releasing peptides that resemble peptide hormones of vertebrates, possibly influencing host cell function.


Audit of advice provided on pelvic floor exercises.
Stress incontinence is often seen as an inevitable consequence of childbirth rather than a condition that is both preventable and treatable. Pelvic floor exercises can reduce the symptoms of urinary incontinence. An audit of provision of pelvic floor exercise-related advice revealed that more high-quality information was needed.


Effects of acupuncture at Baihui (GV 20) and Zusanli (ST 36) on peripheral serum expression of MicroRNA 124, laminin and integrin β1 in rats with cerebral ischemia reperfusion injury.
To explore the effects of acupuncture at Baihui (GV 20) and Zusanli (ST 36) on the peripheral serum expression of microRNA 124 (miRNA 124), laminin and integrin β1 in rats with cerebral ischemia reperfusion injury (CIRI). Seventy-two healthy male Sprague-Dawley rats were randomized into a model group, an acupuncture group, and a sham-operated group using a random digits table, with 24 rats per group. Each group was further randomly divided into 1-, 3-, 5-, and 7-day subgroups based on the reperfusion time according to a random digits table, with 6 rats in each subgroup. In the model and acupuncture groups, CIRI was induced using the thread occlusion method. Electroacupuncture stimulation was applied daily to GV 20 and left ST 36 for 20 min at the indicated time points after successful operations. Serum was sampled for detecting laminin and integrin β1 protein via enzyme-linked immunosorbent assay, and serum miRNA 124 was examined using quantitative polymerase chain reaction. The serum level of miRNA 124 in the cerebral ischemia rats increased significantly, and the peak expression of miRNA 124 in both the model and acupuncture groups occurred at 3 days. The expression of miRNA 124 in the acupuncture group was higher than in the model group at the same time point (5.96±0.01 vs. 3.11±0.04, P <0.05). Laminin expression in serum from the cerebral ischemia group was higher than that in the sham-operated group. Compared with the model group, the level of laminin in the serum of the acupuncture group was significantly lower at each time point, especially at the 3-day, and 7-day time points (589.12±3.57 vs. 793.05±5.28, and 600.53±3.05 vs. 899.06±5.74, P <0.05). The level of integrin β1 in the serum from the acupuncture group was lower than that in the model group particularly at the 3-day and 7-day time points (208.66±0.95 vs. 280.83±1.77, and 212.36±0.95 vs. 316.77±2.42, P <0.05). Additionally, the model group and the acupuncture group showed dual peaks of integrin β1 and laminin expression at 3-day and 7-day. Acupuncture at GV 20 and ST 36 in rats alleviated CIRI and was associated with upregulated expression of miRNA 124 and with downregulated expression of integrin β1 and laminin in peripheral serum. These changes may represent one of the mechanisms underlying acupuncture's attenuation of CIRI.


Direct electron transfer and electrocatalysis of hemoglobin adsorbed on coralloid gold nanostructures.
Three-dimensional (3D) coralloid gold nanostructures (CGNs) have been fabricated by using an electrochemical growth method on the ITO glass substrates coated with agarose gel. Characterization by a variety of complementary techniques including scanning electron microscopy (SEM), X-ray diffraction (XRD), and UV-vis spectroscopy confirmed the distribution of CGNs on the ITO glass substrates. The adsorption behaviors of hemoglobin (Hb) on the CGNs-modified ITO (CGNs/ITO) electrodes were investigated by UV-vis spectroscopy and electrochemical methods, and the results demonstrated that 3D CGNs could provide good microenvironment for loading biomolecules and retaining their biological activity. Direct electron transfer of the adsorbed Hb exhibited a couple of stable and well-defined redox peaks centered at about -0.121 V and -0.041 V (vs. SCE) in 0.1 mol L(-1) pH 7.0 PBS. The electron transfer rate constant is 0.78 s(-1) at a scan rate of 0.1 V (s-1). The adsorbed Hb in the CGNs displayed a rapid amperometric response to the reduction of hydrogen peroxide (H2O2) for a broad linear range from 1.0 x 10(-6) mol LV(-1) to 5.0 x 10(-3) mol L(-1) with the detection limit of 3.0 x 10(-7) mol L(-1) (S/N = 3).


Evolution of pulmonary function after treatment with goserelin in patients with lymphangioleiomyomatosis.
In the atypical smooth muscle cells that are characteristic of lymphangioleiomyomatosis (LAM), there are estrogen and progesterone receptors. Therefore, anti-hormonal therapy, despite having produced controversial results, can be considered a treatment option. The objective of this retrospective study was to evaluate hormonal and spirometric data for nine women with LAM after one year of treatment with goserelin. The mean increase in FEV1 and FVC was 80 mL and 130 mL, respectively. There was effective blockage of the hormonal axis. It is still not possible to exclude a potential beneficial effect of the use of gonadotropin-releasing hormone analogues in LAM patients, which underscores the need for randomized trials.


Visible light decomposition of ammonia to N2 with Ru(bpy)3(2+) sensitizer.
Visible light decomposition of aqueous NH3 to N2 was investigated using a photocatalyst aqueous solution based on molecular photoelectron relay systems of either sensitizer (tris(2,2'-bipyridine)ruthenium(II), (Ru(bpy)3(2+))/potassium peroxodisulfate(K(2)S(2)O(8)) or Ru(bpy)3(2+)/methylviologen dichloride(MV2+)/O2, capable of using visible light instead of UV-driven semiconductors such as TiO2. It was confirmed by using an in situ visible absorption spectral change under irradiation that the Ru(II) complex is oxidized to the Ru(III) complex by K(2)S(2)O(8), and that the Ru(III) complex formed is stable without NH3, while the added NH3 was oxidized by the Ru(III) complex to produce the Ru(II) complex. In the presence of 1 mM NH3 aqueous solution, the Ru(III) complex was the predominant species under the photostationary state, but in the presence of 100 mM NH3, Ru(II) predominated. Gas-chromatographic analysis of the gaseous phase in the presence of 8.1 M NH3 showed that the photochemical oxidation of ammonia yielded N2. It was also demonstrated by using the in situ visible absorption spectrum under irradiation of the NH3 (1 M)/Ru(bpy)3(2+) (0.1 mM)/MV2+ (10 mM) system under Ar that MV+* is accumulated, showing that NH3 works as an electron donor for MV+* accumulation with simultaneous formation of the oxidized product of ammonia ((NH3)ox) without producing N2. It was suggested that the reduced product (MV+*) and the oxidized product ((NH3)ox) are in a kind of dynamic equilibrium prohibiting further oxidation of (NH3)ox by Ru(bpy)3(3+) to N2. In the O2 atmosphere, the oxidation of MV+* to MV2+ takes place to accumulate Ru(III) complex, so that (NH3)ox was further oxidized to N2. The high activity of IrO2 as a cocatalyst in this system was demonstrated.


Phosphoenolpyruvate-dependent flavinylation of 6-hydroxy-D-nicotine oxidase.
The reaction leading to the flavinylation of apo-6-hydroxy-D-nicotine oxidase was investigated in cell-free extracts of Eschericia coli carrying the 6-hydroxy-D-nicotine oxidase (6-HDNO) gene on the expression plasmid pDB222. It was demonstrated that the reaction required phosphoenolpyruvate (P-pyruvate) in addition to FAD. When [32P]P-pyruvate or [14C]P-pyruvate were used in the reaction with apo-6-HDNO, no phosphorylated or pyruvylated apo-protein could be detected, however. In order to drive the reaction to completion, FAD and P-pyruvate had to be present simultaneously in the reaction mixture. When apo-6-HDNO, highly purified by affinity chromatography, was used in the reaction with P-pyruvate and FAD, no additional protein fraction was required. A possible reaction scheme for the formation of holoenzyme from 6-HDNO is discussed.


Research capacity strengthening for sexual and reproductive health: a case study from Latin America.
An essential, but often overlooked part of health promotion and development support to achieve self-sufficiency in developing countries is the concomitant need to build and strengthen research capacity. This is even more challenging and critical in the area of sexual and reproductive health because of diverse interplay of socio cultural, religious, economic factors in relation to reproductive health.This paper presents the case study of HRP's efforts to build research capacity in Latin America by studying and analyzing the 5-year history of institutional development support to an institution in Paraguay. In reviewing the efforts, we identify the strengths in the approaches used by HRP, the challenges and outcomes of the process and we present recommendations for future efforts to strengthen research capacity to improve sexual and reproductive health. The authors call for greater support from and collaborative efforts of developmental partners and governments to strengthen research capacity in low and middle-income countries to improve sexual and reproductive health.


Peritonitis rates for CAPD patients using the SCD 210 (Inpersol sterile connecting device): a Canadian survey.
A retrospective study was conducted in 20 Canadian hospitals to assess peritonitis rates of CAPD patients utilizing the SCD 210 patient assist device during a 30 month study period. A total of 175 patients having a cumulative SCD experience of 1,494 patient months were included in the survey. Sixty-eight patients experienced 116 episodes of peritonitis, i.e., one episode every 12.9 patient months (pt mo). Patients that had used the SCD for their entire CAPD experience had a significantly lower peritonitis rate (1/15.2 pt mo) compared to patients who had used other CAPD systems (1/10.1 pt mo). Peritonitis rates for diabetic study patients or patients with impaired vision and/or dexterity were not significantly greater than non-diabetic or non-impaired study patients. Staphylococcus epidermidis and Staphylococcus aureus were the most frequent causative microorganisms, accounting for 27.7% and 16.0% of peritonitis episodes caused by single organisms, respectively. The proportion of peritonitis caused by skin commensals was consistent across all study patients, regardless of impairment of vision and/or dexterity. The study results demonstrate the successful application of this patient assist device in a CAPD population that consisted of a large proportion of high risk patients.


Isolation of a DNA-binding protein from Deinococcus radiodurans having an affinity for a Z-form polynucleotide.
A protein which preferentially binds Z-form duplex DNA has been purified from the cells of Deinococcus radiodurans. The molecular weight of the protein was estimated to be approximately 68,000 by gel filtration and SDS-polyacrylamide gel electrophoresis. Amino acid analysis of the protein indicates that it is not so basic since it contains a lower mole percent of lysine and higher mole percent of aspartic acid than those in histone-like DNA binding protein II (HU) of Escherichia coli. The first fifteen amino acid residues from the N-terminus have been also determined.


Homo- and heteroleptic complexes of four-membered group 13 metal(I) N-heterocyclic carbene analogues with group 10 metal(0) fragments.
A series of complexes between recently developed four-membered group 13 metal(I) heterocycles and group 10 metal(0) fragments have been prepared and structurally characterized. One prepared complex, [Pt{Ga[N(Ar)]2CNCy2}3] (Ar = C6H3Pri2-2,6; Cy = cyclohexyl), possesses the shortest Pt-Ga bonds yet reported, the covalent components of which are suggested by theoretical studies to have significant pi character.


Changes in bioavailability and tissue distribution of zinc caused by magnesium deficiency in rats.
The effect of a Mg-deficient diet (200 mg Mg/kg feed) on the bioavailability of dietary Zn and the concentration of this cation in plasma, whole blood, skeletal muscle, kidney, heart and brain of Wistar rats was studied after 7, 35, 42, 49, 56, 63 and 70 d. Mg deficiency significantly decreased Zn in whole blood on day 42 of the experiment, but there was no significant change in plasma Zn throughout the 70 d study period. The Mg-deficient diet significantly increased intestinal absorption of Zn, Zn balance, and Zn concentration in femur and kidney, but decreased Zn concentration in the heart despite the increase in dry weight of this organ. No change was found in brain Zn concentration.


Vasorin, a transforming growth factor beta-binding protein expressed in vascular smooth muscle cells, modulates the arterial response to injury in vivo.
Growth factors, cell-surface receptors, adhesion molecules, and extracellular matrix proteins play critical roles in vascular pathophysiology by affecting growth, migration, differentiation, and survival of vascular cells. In a search for secreted and cell-surface molecules expressed in the cardiovascular system, by using a retrovirus-mediated signal sequence trap method, we isolated a cell-surface protein named vasorin. Vasorin is a typical type I membrane protein, containing tandem arrays of a characteristic leucine-rich repeat motif, an epidermal growth factor-like motif, and a fibronectin type III-like motif at the extracellular domain. Expression analyses demonstrated that vasorin is predominantly expressed in vascular smooth muscle cells, and that its expression is developmentally regulated. To clarify biological functions of vasorin, we searched for its binding partners and found that vasorin directly binds to transforming growth factor (TGF)-beta and attenuates TGF-beta signaling in vitro. Vasorin expression was down-regulated during vessel repair after arterial injury, and reversal of vasorin down-regulation, by using adenovirus-mediated in vivo gene transfer, significantly diminished injury-induced vascular lesion formation, at least in part, by inhibiting TGF-beta signaling in vivo. These results suggest that down-regulation of vasorin expression contributes to neointimal formation after vascular injury and that vasorin modulates cellular responses to pathological stimuli in the vessel wall. Thus, vasorin is a potential therapeutic target for vascular fibroproliferative disorders.


Granular cell ameloblastoma: case report of a particular ameloblastoma histologically resembling oncocytoma.
Granular cell ameloblastoma is classified as a histological subtype of solid/multicystic ameloblastoma. Usual granular cell ameloblastoma is histologically characterized by granular changes of stellate-like cells located in the inner portion of the epithelial follicles. Here we report a case of another type of granular cell ameloblastoma, showing predominant anastomosing double-stranded trabeculae of granular cells. This type of granular cell ameloblastoma is extremely rare, and the World Health Organization classification does not contain the entity. We tentatively termed it 'anastomosing granular cell ameloblastoma' in this report. The present case suggests the importance of differential diagnosis because the histology of 'anastomosing granular cell ameloblastoma' resembles that of salivary gland oncocytoma rather than that of usual granular cell ameloblastoma. The trabeculae observed in our case continued to the peripheral cells of a small amount of epithelial sheets of plexiform ameloblastoma, and the tumor cells were positive for CK19, which is regarded as an immunohistochemical marker of odontogenic epithelium. Similar to usual granular cell ameloblastoma, the tumor cells had CD68-positive granules. For precise diagnosis of this condition, immunohistochemistry using CK19 and CD68, as well as detailed histological observation, are recommended.


Phenylene Bridged Cyclic Azaacenes: Dimers and Trimers.
The synthesis and characterization of novel macrocyclic, phenylene-bridged azaacenes is reported. These species were obtained either by a conventional benzoin- diamine condensation, as shown for the case of the cyclotrimers, in which the azaacene units are separated by meta-connected phenylene bridges, or by a Buchwald-Hartwig-type Pd-catalyzed coupling, which employs 1,2,5,6-tetrabromodibenzocyclooctatetraene as the substrate and bis-TIPS-ethynylated diaminobenzene, -naphthalene or -anthracene as the coupling partner to give the double coupling products azaacene-annulated dibenzocyclooctatetraenes in moderate yields. The macrocycles show strong emission and light emitting diodes have been built with brightnesses exceeding 1600 cd m-2 . We evaluated the optical and electronic properties and the solid-state structures of the molecules and discuss their properties through comparison with their linear and tetrameric N-heteroacene counterparts.


Hip arthroscopy for excision of osteoid osteoma and for the application of a collagen cartilage implant: Case report in a professional athlete, and literature review.
Osteoid osteoma is an osteoblastic benign bone tumor usually affecting young adolescents. Intra-articular lesions are not common; usually the diagnosis is delayed. A lot of studies report difficulties and complications in the management of osteoid osteoma of the hip joint using imaging guided techniques or open surgical procedures. Only few published cases have described that it can be treated precisely using hip arthroscopy. Additionally, the use of hip arthroscopy to apply the Chondrofiller®, an acellular collagen matrix for the management of articular cartilage defects of the hip joint, has not yet been described. This report presents an osteoid osteoma of the femoral neck. A 20-year-old female professional basketball player presented with pain in the left groin since more than 12 months. On magnetic resonance and computed tomography imaging, an osteoid osteoma was suggested. The lesion was successfully removed using arthroscopy. During surgery, a concomitant grade 4 cartilage lesion on the femoral head was detected. For the treatment of this severe defect we used the Chondrofiller®, which is a new acellular collagen implant for auto-regeneration of articular cartilage. This matrix was filled into the prepared and dried defect using CO2 arthroscopy. After the hardening of the matrix the surgery was finished. The patient was pain free shortly after the operation and returned to sports within 16 weeks. Return to high-performance sports 8 months after surgery was without of any sign of complaints. This article demonstrates that hip arthroscopy is a valuable tool for biopsy and excision of intra-articular osteoid osteoma affecting the hip joint, as well as for addressing other concomitant pathologies such as a severe synovitis or cartilage defects. CO2 arthroscopy provided good conditions for the drying and filling of the cartilage defect with the Chondrofiller®.


Are general surgeons able to accurately self-assess their level of technical skills?
Self-assessment is a way of improving technical capabilities without the need for trainer feedback. It can identify areas for improvement and promote professional medical development. The aim of this review was to identify whether self-assessment is an accurate form of technical skills appraisal in general surgery. The PubMed, MEDLINE(®), Embase(™) and Cochrane databases were searched for studies assessing the reliability of self-assessment of technical skills in general surgery. For each study, we recorded the skills assessed and the evaluation methods used. Common endpoints between studies were compared to provide recommendations based on the levels of evidence. Twelve studies met the inclusion criteria from 22,292 initial papers. There was no level 1 evidence published. All papers compared the correlation between self-appraisal versus an expert score but differed in the technical skills assessment and the evaluation tools used. The accuracy of self-assessment improved with increasing experience (level 2 recommendation), age (level 3 recommendation) and the use of video playback (level 3 recommendation). Accuracy was reduced by stressful learning environments (level 2 recommendation), lack of familiarity with assessment tools (level 3 recommendation) and in advanced surgical procedures (level 3 recommendation). Evidence exists to support the reliability of self-assessment of technical skills in general surgery. Several variables have been shown to affect the accuracy of self-assessment of technical skills. Future work should focus on evaluating the reliability of self-assessment during live operating procedures.


Changes in climate and land use have a larger direct impact than rising CO2 on global river runoff trends.
The significant worldwide increase in observed river runoff has been tentatively attributed to the stomatal "antitranspirant" response of plants to rising atmospheric CO(2) [Gedney N, Cox PM, Betts RA, Boucher O, Huntingford C, Stott PA (2006) Nature 439: 835-838]. However, CO(2) also is a plant fertilizer. When allowing for the increase in foliage area that results from increasing atmospheric CO(2) levels in a global vegetation model, we find a decrease in global runoff from 1901 to 1999. This finding highlights the importance of vegetation structure feedback on the water balance of the land surface. Therefore, the elevated atmospheric CO(2) concentration does not explain the estimated increase in global runoff over the last century. In contrast, we find that changes in mean climate, as well as its variability, do contribute to the global runoff increase. Using historic land-use data, we show that land-use change plays an additional important role in controlling regional runoff values, particularly in the tropics. Land-use change has been strongest in tropical regions, and its contribution is substantially larger than that of climate change. On average, land-use change has increased global runoff by 0.08 mm/year(2) and accounts for approximately 50% of the reconstructed global runoff trend over the last century. Therefore, we emphasize the importance of land-cover change in forecasting future freshwater availability and climate.


Role of cellular retinoic acid binding protein (cRABP) in patients with large bowel cancer.
The presence of cellular retinoic acid binding protein (cRABP) was analyzed in 13 consecutive patients with large bowel cancer (one right colon and 12 rectum-sigmoid, classified as three Duke B, eight C, and two D). Specimens of neoplastic tissue and of adjacent mucosa were obtained at surgery, and cRABP was determined by an assay based on incubation of partially purified cytosol with labeled retinoic acid and ultracentrifugation in sucrose density gradients. Sixty-one percent of tumors contained detectable levels of cRABP, whereas 58.3% of normal mucosal specimens were positive for cRABP. Among the positive tumors 62.5% contained cRABP also in the corresponding mucosa; in the group of cRABP-negative tumors, 40% showed cRABP in the adjacent mucosa. No correlation could be established with the grading or the stage of the tumors; however, interestingly, 100% (three cases) of gelatinous carcinomas were cRABP positive. Since cRABP seems to be a character of neoplastic cells contrary to normal ones, it would be interesting to investigate the conditions that influence the presence of this protein in normal appearing mucosa adjacent to carcinoma.


Regulation of calcium fluxes in pancreatic islets: glucose-induced calcium-calcium exchange.
Glucose provokes an initial fall followed by a secondary rise in 45Ca efflux from prelabeled pancreatic islets. Prior exposure of the islets to calcium-depleted media does not suppress the secondary rise, provided that the extracellular calcium concentration is normalized 2 min before addition of glucose. Such a treatment significantly reduces insulin release. The secondary rise, as distinct from the initial fall, is inhibited under conditions known to interfere with calcium entry into the beta-cell, e.g., in the presence of ruthenium red or cobalt. Calcium itself in high concentrations provokes a dramatic increase in 45Ca efflux. The magnitude of this calcium-induced efflux is enhanced by prior exposure of the islets to calcium-depleted media. Imidazole and the theophylline do not modify the effect of glucose on 45Ca efflux. It is proposed that the glucose-induced secondary rise in 45Ca efflux corresponds to a calcium-calcium exchange process in which influent 40Ca displaces 45Ca from intracellular sites.


A Polyphenol-rich Pomegranate Fruit Extract Suppresses NF-κB and IL-6 Expression by Blocking the Activation of IKKβ and NIK in Primary Human Chondrocytes.
Pomegranate fruit extract (PE) rich in polyphenols has been shown to exert chondroprotective effects, but the mechanism is not established. Here, we used an in vitro model of inflammation in osteoarthritis (OA) to investigate the potential of PE to suppress interleukin 1 beta (IL-1β)-stimulated expression of inflammatory cytokine IL-6, generation of reactive oxygen species (ROS) levels, and investigated the mechanism of NF-κB inhibition by analyzing the activation of the kinases upstream of IκBα in primary human chondrocytes. Total and phosphorylated forms of kinases and expression of IL-6 were determined at protein and mRNA levels by western immunoblotting and Taqman assay, respectively. Dihydrorhodamine 123 staining estimated ROS generation. Pomegranate fruit extract inhibited the mRNA and protein expression of IL-6, generation of ROS, and inhibited the IL-1β-mediated phosphorylation of inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ), expression of IKKβ mRNA, degradation of IκBα, and activation and nuclear translocation of NF-κB/p65 in human chondrocytes. Importantly, phosphorylation of NF-κB-inducing kinase was blocked by PE in IL-1β-treated human OA chondrocytes. Taken together, these data suggest that PE exerts the chondroprotective effect(s) by suppressing the production of IL-6 and ROS levels. Inhibition of NF-κB activation by PE was blocked via modulation of activation of upstream kinases in human OA chondrocytes. Copyright © 2017 John Wiley & Sons, Ltd.


Surgical correction of pulmonary artery aneurysm with extrinsic compression of the left main coronary artery: A case report.
Pulmonary artery aneurysm (PAA) is a rare disease, with a poorly known natural history, complex diagnosis and may evolve with serious complications, such as compression of adjacent anatomical structures. In some cases, the presence of such complications is what determines the symptoms and is the initial manifestation of the disease. This paper aims to report the case of a patient with typical angina, submitted to cardiac catheterization, which showed, among other lesions, severe left main coronary lesion with characteristics that led to the suspicion of extrinsic compression, which was identified as caused by a PAA. The treatment chosen in this case was surgical, reported concurrently with a literature review that guided the medical team in their decision-making. Surgical correction of PAA may provide resolution of coronary symptoms in affected individuals.


Percutaneous Superficial Medial Collateral Ligament Release Outcomes During Medial Meniscal Arthroscopy: A Systematic Review.
To systematically review the literature to better understand the technique, outcomes, and complications after percutaneous superficial medial collateral ligament (sMCL) lengthening during knee arthroscopy to address isolated medial meniscal pathology. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using a PRISMA checklist. The inclusion criteria consisted of English-language articles or articles with English-language translations documenting the use of percutaneous sMCL lengthening during arthroscopic knee surgery to treat isolated meniscal pathology (repair vs meniscectomy) with reported postoperative outcomes and complications. Four studies met the inclusion criteria, consisting of a total of 192 patients undergoing percutaneous sMCL lengthening. No perioperative complications related to iatrogenic chondral damage, fracture, or additional meniscal injury were reported. Mild postoperative pain at the medial needle tract site lasting up to 15 days after surgery was reported in 52% of patients (46 of 88). At final follow-up, laxity on valgus stress testing showed a range from 0 to 1.1 mm with a range from -0.3° to 0.9° of radiographic medial joint space widening compared with preoperative radiographs. The length of follow-up ranged from 1.5 to 24 months. The percutaneous "pie-crusting" technique remains the most commonly reported technique to lengthen the sMCL during arthroscopic meniscal surgery. Percutaneous lengthening represents a safe and effective method of increasing medial joint space visualization, with no reported perioperative or postoperative complications and with minimal, likely clinically insignificant residual joint laxity after surgery on valgus stress testing at final follow-up compared with preoperative values. Level IV, systematic review of Level IV studies.


Postnatal maturation of somatostatin-expressing inhibitory cells in the somatosensory cortex of GIN mice.
Postnatal inhibitory neuron development affects mammalian brain function, and failure of this maturation process may underlie pathological conditions such as epilepsy, schizophrenia, and depression. Furthermore, understanding how physiological properties of inhibitory neurons change throughout development is critical to understanding the role(s) these cells play in cortical processing. One subset of inhibitory neurons that may be affected during postnatal development is somatostatin-expressing (SOM) cells. A subset of these cells is labeled with green-fluorescent protein (GFP) in a line of mice known as the GFP-positive inhibitory neurons (GIN) line. Here, we studied how intrinsic electrophysiological properties of these cells changed in the somatosensory cortex of GIN mice between postnatal ages P11 and P32+. GIN cells were targeted for whole-cell current-clamp recordings and ranges of positive and negative current steps were presented to each cell. The results showed that as the neocortical circuitry matured during this critical time period multiple intrinsic and firing properties of GIN inhibitory neurons, as well as those of excitatory (regular-spiking [RS]) cells, were altered. Furthermore, these changes were such that the output of GIN cells, but not RS cells, increased over this developmental period. We quantified changes in excitability by examining the input-output relationship of both GIN and RS cells. We found that the firing frequency of GIN cells increased with age, while the rheobase current remained constant across development. This created a multiplicative increase in the input-output relationship of the GIN cells, leading to increases in gain with age. The input-output relationship of the RS cells, on the other hand, showed primarily a subtractive shift with age, but no substantial change in gain. These results suggest that as the neocortex matures, inhibition coming from GIN cells may become more influential in the circuit and play a greater role in the modulation of neocortical activity.


Polymorphism of the Fcγ Receptor II as a Possible Predisposing Factor for Heparin-Induced Thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) represents a serious complication of heparin treatment. IgG antibodies binding platelet factor 4 (PF4) and heparin trigger the clinical manifestations of HIT. However, only a portion of the antibodies have the ability to activate platelets, and these can be identified by a platelet aggregation test (functional testing). However, this expression has been detected to have a molecular cause, which is a mutation of FcγRIIa. The FcγRIIa receptor is responsible for the activation of platelets by antibodies in HIT. To determine HIT, impedance aggregometry using the Multiplate analyzer (MEA) as heparin-induced aggregation technique and the Technozym HIT IgG ELISA test were used. The MEA method uses sensitization of donor platelets with patient plasma in the presence of heparin at a concentration of 0.5 IU/mL. The results were compared with the ELISA test. Mutation of FcγRHa was assessed using the asymmetric real-time PCR method that is based on the reaction with two hybridization probes and melting curve analysis. Examined were 100 patients at a clinically intermediate and higher risk of HIT according to the 4T's score. All samples were examined by the ELISA test and MEA, with positive samples being further confirmed by high-concentration heparin. In the group of patients, 10.0% were positive by MEA as compared with 4% determined by ELISA. The results of genetic analysis of FcγRIIa did not provide statistically significant differences between positive patients found by the functional test as well as the ELISA test and seronegative patients. The genetic mutation FcγRIIa is a predisposing factor for manifestation of HIT in the form of thrombocytopenia, but the process of seroconversion apparently needs another inducing factor. Therefore, the examination of mutations can be classified as predisposing factors rather than to confirm the diagnosis of HIT.


A Long-Cycle-Life Self-Doped Polyaniline Cathode for Rechargeable Aqueous Zinc Batteries.
Rechargeable aqueous zinc batteries are promising energy-storage systems for grid applications. Highly conductive polyaniline (PANI) is a potential cathode, but it tends to deactivate in electrolytes with low acidity (i.e. pH >1) owing to deprotonation of the polymer. In this study, we synthesized a sulfo-self-doped PANI electrode by a facile electrochemical copolymerization process. The -SO3 - self-dopant functions as an internal proton reservoir to ensure a highly acidic local environment and facilitate the redox process in the weakly acidic ZnSO4 electrolyte. In a full zinc cell, the self-doped PANI cathode provided a high capacity of 180 mAh g-1 , excellent rate performance of 70 % capacity retention with a 50-fold current-density increase, and a long cycle life of over 2000 cycles with coulombic efficiency close to 100 %. Our study opens a door for the use of conducting polymers as cathode materials for high-performance rechargeable zinc batteries.